Suppression of human prostate carcinoma metastases in severe combined immunodeficient mice by interleukin 2 immunocytokine therapy

Immunocytokines are antibody-cytokine fusion proteins that combine the unique targeting ability of antibodies with the multifunctional activities of cytokines to activate effector cells in the tumor microenvironment. Here, we demonstrate the therapeutic efficacy of a tumor-specific immunocytokine, huKS1/4-IL2, which effectively inhibited growth and dissemination of lung and bone marrow metastases of human prostate carcinoma in severe combined immunodeficient mice. This antitumor effect was specific and highly effective, irrespective of reconstitution of these mice with human lymphokine-activated killer cells. Survival times of mice treated with huKS1/4-IL2 were increased 4-fold as compared with animals treated with a mixture of the corresponding antibody and recombinant human interleukin-2 (rhIL2). A persistent antitumor response after treatment with the huKS1/4-IL2 immunocytokine in B, T, and natural killer cell-deficient severe combined immuodeficient-BEIGE mice, depleted of granulocytes, implies a major role for macrophages in this treatment effect. Our data demonstrate that immunocytokine-directed interleukin-2 therapy to tumor sites is an immunotherapeutic approach with potent effects against disseminated metastases of human prostate carcinoma and suggest that this treatment could be effective in an adjuvant setting for patients with minimal residual disease.     

Influence of porcine somatotropin on the phosphorus requirement of finishing pigs: I. Performance and bone characteristics

We conducted two experiments to evaluate the effects of recombinant porcine somatotropin (pST) on the P requirement of finishing pigs. Corn-soybean meal diets with varying levels of P were fed, and Ca was adjusted to maintain a Ca:P ratio of 1.1:1. In Exp. 1, 96 pigs were fed dietary P concentrations of .35, .45, and .65% from 75 to 109 kg BW. One-half of the pigs were injected daily with 4 mg of pST. Pigs treated with pST consumed less feed and gained more efficiently than untreated pigs (P < .01). Increasing the dietary P level produced linear (P < .05) improvements in most metacarpal-metatarsal (MM) and femur traits. Administration of pST increased (P < .02) bone weight, but it reduced (P < .03) bone strength and the percentage of ash. The increases in percentage of ash and ash accretion associated with increasing dietary P were more pronounced in pST-treated pigs than in untreated pigs (pST x P, P < .01). Experiment 2 consisted of 66 pigs fed six dietary P concentrations (.35, .50, .65, .80, .95, and 1.10%) from 72 to 114 kg. One-half of the pigs were injected daily with 4 mg of pST. Pigs treated with pST gained faster and more efficiently (P < .01) but consumed less feed than untreated pigs (P < .01). Increasing the dietary P level improved most of the bone traits. Administration of pST reduced (P < .01) MM strength and percentage ash in the MM and femurs, but it increased (P < .01) femur diameter and wall thickness. Bone strength and percentage ash were reduced in pST-treated pigs fed low dietary P; however, at higher dietary P, these traits were similar to or greater than those in untreated pigs (pST x P, P < .10). Generally, bone traits in pST-treated pigs reached a plateau at higher dietary P concentrations and at higher P intakes compared with those in untreated pigs. These results indicate that pST administration increases the dietary P level that is required to maximize bone traits in finishing pigs.     

Astrocytes are the major source of nerve growth factor upregulation following traumatic brain injury in the rat

A between-side comparison of GABAA receptor subunit expression levels in the globus pallidus and anterior-pole motor thalamic nuclei of rats with an ibotenate lesion of the striatum, and rats receiving a fetal striatal graft in the lesioned area was made by using immunocytochemistry with subunit-specific antibodies, at different times post-lesion or different times post-grafting. At 10 days post-lesion, there was already an increase in the labeling of the alpha 1- and beta 2/3-subunits in the globus pallidus, entopeduncular nucleus and ventrolateral nucleus ipsilateral to the lesion when compared with the contralateral side, while there were no significant changes at the level of the ventromedial nucleus. Labeling of the alpha 2-subunit showed a clear increase in the entopeduncular nucleus compared with the contralateral side at 10 days post-lesion. Similar changes were also observed for the different subunits studied at 30 and 120 days after lesioning. Rats with 20-day old transplants of fetal striatal neurons that were implanted in the ibotenate lesioned striatum at 10 days post-lesioning, continued to show changes in the expression of GABAA receptor subunits, albeit at a lower level than those of ibotenate lesioned rats at similar age post-lesion. However, when examining rats with 70-day old transplants, the ibotenate-lesion induced between-side changes were almost completely compensated. These findings suggest a correlation between the maturation of the grafts and their capability to function in reestablishing neuronal circuits as shown by the reduction of changes in GABAergic transmission induced by ibotenate lesions, as indicated by the reversal of changes in GABAA receptor subunit in several areas of the basal ganglia circuit.     

Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain

More and more elderly subjects are offered for pulmonary resection. The object of this study was to review the results of excision for cancer in octogenarians. PATIENTS: 51 consecutive patients (44 men, 7 women) with a mean age of 82 years (80-91) were operated on. 31 lobectomies, 2 bilobectomies, 13 pneumonectomies, 1 segmental resection and 4 exploratory thoracotomies were carried out. 17 tumours were classed as stage I, 15 as stage II and 15 as stage III. RESULTS: 38 patients (75%) had uncomplicated post-operative periods; the predicted factors for complication were the existence of weight loss and alteration of respiratory function. 2 patients (4%) died in the post-operative phase. Neither the type of operation, the staging or the existence of cardiovascular dysfunction had any influence on the post-operative phase. The level of the survival at 3 and 5 years was 39% and 16% respectively. 30% of the late deaths were related to intercurrent events. CONCLUSIONS: Pulmonary excision may be envisaged in an octogenarian who is in good physical and intellectual state with a limited tumour. This surgery in general is applied to a population which probably only marginally consists of octogenarians but the results here justify their inclusion in the indications for selection.     

Cultured astrocytes express proteins involved in vesicular glutamate release

The objective of this study is to analyze volatile organic compound (VOC) concentrations in Taiwan's drinking water supply. Focusing on Taiwan's three major metropolitan areas--Taipei, Taichung and Kaohsiung (in the north, middle and south, respectively)--171 samples were taken from tap water and 68 from boiled water. Tests showed VOC concentrations were highest in Kaohsiung. This is due to different water sources and methods of treatment. Except for bromoform, trihalomethane (THM) concentrations were highest. Detection rates of toluene and 1,2-dichloroethane were slightly higher than other VOC compounds. VOC concentrations decreased significantly after water was boiled. THMs had a removal rate from 61% to 82%. The authors conclude that the three metropolitan areas contain significantly different levels of VOCs and that boiling can significantly reduce the presence of VOCs. Other sources of pollution that contaminate drinking water such as industrial plants and gas stations must be further investigated.     

The use of ceramic onlays for restoring the occlusal surface of the teeth

Computer-aided milling of ceramic insertions helped more effectively repair the masticatory surface of teeth, minimize the incidence of errors, rule out the laboratory stage of making the insertions and the technological errors made at this stage, retain physical and mechanical characteristics of ceramics, optimize marginal adherence of the insertion to the tooth, retain the height of the lower part of the face, and thus prevent the maxillodental dysfunction.     

Cardiac morphology and left ventricular function in normotensive morbidly obese patients with and without congestive heart failure, and effect of weight loss

BACKGROUND: Prevention of hypothermia during abdominal surgery by insulating or heat-transferring methods has been the subject of numerous investigations. This study approaches the problem from a less discussed point of view, i.e. the effect of different surgical techniques on body temperature changes. METHODS: Body temperature was measured at 3 core and 6 skin points in 40 patients scheduled for cholecystectomy through open laparotomy or laparoscopy with pneumoperitoneum created and maintained with unwarmed carbon dioxide (CO2) insufflation. End-tidal CO2 was kept constant by adjustments of respiratory frequency. Anaesthesia, intravenous infusions, and draping of the patients were standardized. RESULTS: During the first 1 h of anaesthesia core temperatures decreased approximately by 0.7 degrees C and distal skin temperatures increased by 7 degrees C in both groups. At the end of surgery heat balance was similar in both groups. An increase of 2.5 1.min-1 in respiratory minute volume was needed to control end-tidal CO2 levels in the laparoscopy group during pneumoperitoneum which was maintained with a CO2 flow of 1.2 1.min-1 through the abdominal cavity. CONCLUSION: Laparoscopic technique with unwarmed carbon dioxide insufflation does not offer any advantage in terms of body temperature changes when compared to open surgery.